The in vitro activity of ampicillin, amoxicillin/clavulanate, cefadroxil, cefaclor, cefuroxime (axetil), co-trimoxazole, doxycycline, ciprofloxacin, ofloxacin, erythromycin, and roxithromycin was tested against unselected isolates of S. pneumoniae (70), H. influenzae (93), and M. catarrhalis (46), cultured from clinically significant sputum samples of general practice patients. All isolates of S. pneumoniae were highly susceptible to ampicillin; cefadroxil and cefaclor were markedly less active on a weight basis; resistance was only observed with co-trimoxazole (4.3%), doxycycline (5.7%), and erythromycin (2.9%); however, ciprofloxacin and ofloxacin showed median MICs (MIC50), that were only one dilution below breakpoint. Beta-lactamase was detected in 14.0% of H. influenzae isolates; all isolates were susceptible to amoxicillin/clavulanate, cefaclor, and cefuroxime (axetil), although MICs were generally higher for cefaclor; the highest activity was exhibited by ciprofloxacin and ofloxacin; apart from cefadroxil, erythromycin, and roxithromycin, that showed only marginal activity, resistance was observed with co-trimoxazole (4.3%) and doxycycline (1.1%). All (including 71.7% of beta-lactamase producing) isolates of M. catarrhalis were susceptible to amoxicillin/clavulanate, cefaclor and cefuroxime (axetil), although MICs were markedly lower for amoxicillin/clavulanate; ciprofloxacin and ofloxacin showed the lowest MICs; resistance was only observed with cefadroxil (2.2%). In conclusion, the antimicrobial agents showing the most uniformly high in vitro activity against the 3 common community respiratory pathogens tested in the present study, were amoxicillin/clavulanate and, to a lesser extent, cefuroxime (axetil).